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New MraY(AA) Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole

New inhibitors of the bacterial transferase MraY from Aquifex aeolicus (MraY(AA)), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (H324 or H325) of the enzyme active site,...

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Autores principales: Wan, Hongwei, Ben Othman, Raja, Le Corre, Laurent, Poinsot, Mélanie, Oliver, Martin, Amoroso, Ana, Joris, Bernard, Touzé, Thierry, Auger, Rodolphe, Calvet-Vitale, Sandrine, Bosco, Michaël, Gravier-Pelletier, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495235/
https://www.ncbi.nlm.nih.gov/pubmed/36139968
http://dx.doi.org/10.3390/antibiotics11091189
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author Wan, Hongwei
Ben Othman, Raja
Le Corre, Laurent
Poinsot, Mélanie
Oliver, Martin
Amoroso, Ana
Joris, Bernard
Touzé, Thierry
Auger, Rodolphe
Calvet-Vitale, Sandrine
Bosco, Michaël
Gravier-Pelletier, Christine
author_facet Wan, Hongwei
Ben Othman, Raja
Le Corre, Laurent
Poinsot, Mélanie
Oliver, Martin
Amoroso, Ana
Joris, Bernard
Touzé, Thierry
Auger, Rodolphe
Calvet-Vitale, Sandrine
Bosco, Michaël
Gravier-Pelletier, Christine
author_sort Wan, Hongwei
collection PubMed
description New inhibitors of the bacterial transferase MraY from Aquifex aeolicus (MraY(AA)), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (H324 or H325) of the enzyme active site, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin. A panel of ten compounds was synthetized notably thanks to a robust microwave-activated one-step sequence for the synthesis of the oxadiazole ring that involved the O-acylation of an amidoxime and subsequent cyclization. The synthetized compounds, with various hydrophobic substituents on the oxadiazole ring, were tested against the MraY(AA) transferase activity. Although with poor antibacterial activity, nine out of the ten compounds revealed the inhibition of the MraY(AA) activity in the range of 0.8 µM to 27.5 µM.
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spelling pubmed-94952352022-09-23 New MraY(AA) Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole Wan, Hongwei Ben Othman, Raja Le Corre, Laurent Poinsot, Mélanie Oliver, Martin Amoroso, Ana Joris, Bernard Touzé, Thierry Auger, Rodolphe Calvet-Vitale, Sandrine Bosco, Michaël Gravier-Pelletier, Christine Antibiotics (Basel) Article New inhibitors of the bacterial transferase MraY from Aquifex aeolicus (MraY(AA)), based on the aminoribosyl uridine central core of known natural MraY inhibitors, have been designed to generate interaction of their oxadiazole linker with the key amino acids (H324 or H325) of the enzyme active site, as observed for the highly potent inhibitors carbacaprazamycin, muraymycin D2 and tunicamycin. A panel of ten compounds was synthetized notably thanks to a robust microwave-activated one-step sequence for the synthesis of the oxadiazole ring that involved the O-acylation of an amidoxime and subsequent cyclization. The synthetized compounds, with various hydrophobic substituents on the oxadiazole ring, were tested against the MraY(AA) transferase activity. Although with poor antibacterial activity, nine out of the ten compounds revealed the inhibition of the MraY(AA) activity in the range of 0.8 µM to 27.5 µM. MDPI 2022-09-02 /pmc/articles/PMC9495235/ /pubmed/36139968 http://dx.doi.org/10.3390/antibiotics11091189 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wan, Hongwei
Ben Othman, Raja
Le Corre, Laurent
Poinsot, Mélanie
Oliver, Martin
Amoroso, Ana
Joris, Bernard
Touzé, Thierry
Auger, Rodolphe
Calvet-Vitale, Sandrine
Bosco, Michaël
Gravier-Pelletier, Christine
New MraY(AA) Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole
title New MraY(AA) Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole
title_full New MraY(AA) Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole
title_fullStr New MraY(AA) Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole
title_full_unstemmed New MraY(AA) Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole
title_short New MraY(AA) Inhibitors with an Aminoribosyl Uridine Structure and an Oxadiazole
title_sort new mray(aa) inhibitors with an aminoribosyl uridine structure and an oxadiazole
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495235/
https://www.ncbi.nlm.nih.gov/pubmed/36139968
http://dx.doi.org/10.3390/antibiotics11091189
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